Topical drug delivery is a desirable option for formulators seeking a non-invasive, patient-preferred route of administration. Like oral administration, topical drug products are easy for the patient to dose at home and are typically painless. However, despite its advantages – such as bypassing the gastrointestinal (GI) tract – special consideration must be taken when formulating topical treatments.

As a result, formulators are increasingly looking to multifunctional excipients in tandem with emerging drug delivery technologies to provide solutions. One such excipient group that has found success in topical drug delivery systems are Carbopol^® polymers. The physicochemical properties exhibited by Carbopol® polymers, such as their gel-forming capacity, viscoelastic nature in a final formulation, and thermal stability, combined with their high compatibility with a variety of active pharmaceutical ingredients (APIs), make them a versatile excipient class for innovative topical formulations. In this blog, we will examine three application areas with examples from recent literature where Carbopol® polymers are supporting the development of drug products to overcome the traditional challenges associated with topical delivery.

Liposomes

Carbopol^® polymers can be applied in liposome-based technologies. Liposomes are phospholipid nano-carriers that can be used for targeted drug delivery. They consist of a bilayer membrane comprised of hydrophobic molecules, with hydrophilic molecules entrapped in the aqueous center. Liposomes offer several advantages over traditional methods of drug delivery including higher biocompatibility, the capacity for self-assembly, and the ability to carry large drug payloads.¹

The use of Carbopol^® polymers as gelling agents in liposome-based medicines is beneficial, as they can dynamically regulate the release of the entrapped drug to a site of action directly. ² When the liposomes were incorporated into a gel formulation containing Carbopol^® polymers, the drug delivery to the deeper skin layers was further enhanced by improving the contact time and avoiding water loss from the skin.³

Carbopol^® polymers are compatible with many APIs and have shown the ability to not only successfully impart desired physical properties in liposome-based drug delivery systems, but also improve drug release. There is great potential for further innovation using Carbopol^® polymers in the liposome drug delivery field.

Mucoadhesive In Situ Gelling Systems

Mucoadhesive in situ gelling systems offer promising potential to overcome drawbacks of conventional mucosal drug delivery formulations, such as poor mucous membrane permeation and remaining at the target site for an insufficient duration of time. Another major advantage of these systems is that they can be administered as a liquid, and later form a gel at the target site. This results in a system that has increased resistance to flow and prolonged duration at the site of action.⁴

Carbopol^® polymers have the desired mucoadhesive properties required for use in mucoadhesive in situ gelling systems.⁵ Due to the structure of Carbopol® polymers, they also contribute to gelling properties. Carbopol^® polymers have high molecular weight and a high percentage of carboxylic groups available to form hydrogen bonding and/or macromolecular interchain penetration with mucous membranes. When evaluated using an in vitro oesophageal retention model, Carbopol^® polymers showed significantly longer retention on simulated mucosal tissues than other mucoadhesive excipients such as xanthan, carrageenan and sodium carboxymethylcellulose.⁶

As a result of their superior mucoadhesive properties, Carbopol^® polymers have been utilized in various mucoadhesive in situ gelling systems along with thermogelling polymers to aid formulation. One such example is the use of Carbopol^® 974P NF polymer and a thermogelling polymer poloxamer 407 in situ nasal gels for the treatment of allergic rhinitis. The Carbopol^® polymer’s mucoadhesive properties increased the duration of the drug at the active site and prolonged drug release in vitro.⁷ In another example, Carbopol® polymers were added to suppositories alongside thermosensitive polymers to form in situ gels 8 The polymer combinations gave synergistic benefits, such as increased gel strength, as well as improving drug retention at the active site.

Antimicrobials

Topical antimicrobials, especially for use in wound care and skin infection applications, are a well-established treatment. However, ensuring effective dosage can still present a challenge to formulators.

Carbopol^® polymers have been formulated as excipients in many topical antimicrobial drug products containing APIs such as azithromycin, ciclopirox, clindamycin, clotrimazole, erythromycin, fusidic acid, ganciclovir, metronidazole, and naftifine. This indicates that Carbopol® polymers are compatible with a broad range of antimicrobial drugs and enable their antimicrobial activity.⁸

Furthermore, compositions containing Carbopol^® polymers have demonstrated potential therapeutic benefits in the prevention or treatment of acute viral infection and/or allergenic infections or conditions. A recent patent exhibited various methods and compositions that may be used for the prevention or treatment of the common cold, as well as allergen-induced conditions such as allergic rhinitis. It was found that pH-neutral compositions containing Carbopol^® 980 NF and 981 NF polymers contributed to reduced viral or allergenic activity in mammalian epithelial cells in vitro, indicating a therapeutic utility for the topical, and especially intranasal, treatment of viral infection and/or allergenic conditions.⁹

These examples emphasize the opportunities that Carbopol^® polymers present in the field of topical antimicrobials.

Enablers of Pharmaceutical Innovation: Carbopol^® Polymers and LLS Health

This blog reviewed three unique application areas in literature where Carbopol^® polymers supported the development of topical drug delivery systems in new and exciting uses, but this is just a small sample of what these excipients can enable. The versatility and efficacy of Carbopol^® polymers make them the ideal excipient for innovation.

LLS Health has decades of experience in producing quality excipients for drug development and has a dedicated team of scientists to support our customers. We work to ensure that pharma manufacturers experience an unhindered process for the development and commercialization of pharmaceutical products.

For more information visit: https://www.lubrizol.com/Health/Pharmaceuticals/Excipients/Carbopol-Polymer-Products

*Though several reference papers mentioned in this blog might include benzene-polymerized carbomers, Lubrizol no longer recommends the use of benzene-polymerized carbomers in pharmaceutical formulations. This table found on our website shows recommended substitutes for the benzene grade Carbopol® polymers based on viscosity criteria.

References*

Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S. Y.; Sood, A. K.; Hua, S. Advances and Challenges of Liposome Assisted Drug Delivery. Front. Pharmacol. 2015, 6.

Yadav, K.; Soni, A.; Singh, D.; Singh, M. R. Polymers in Topical Delivery of Anti-Psoriatic Medications and Other Topical Agents in Overcoming the Barriers of Conventional Treatment Strategies. Prog. Biomater. 2021, 10, 1–17. https://doi.org/10.1007/s40204-021-00154-7.

Shah PP, Desai PR, Patel AR, Singh MS (2012) Skin permeating nanogel for the cutaneous co-delivery of two anti-infammatory drugs. Biomaterials 33:1607–1617

Forouhe Zahir-Jouzdani, Julian Dominik Wolf, Fatemeh Atyabi & Andreas Bernkop-Schnürch; In situ gelling and mucoadhesive polymers: why do they need each other?, Expert Opinion on Drug Delivery, 2018, 15 (10), 1007-1019,

Kumar S. and Himmelstein K. J; Modification of in Situ Gelling Behaviour of Carbopol Solutions by Hydroxypropyl Methylcellulose. J. Pharm. Sci, 1995, 84 (3), 344-348

Mucoadhesive polymers in pharmaceutical formulations - lubrizol. Mucoadhesive Polymers in Pharmaceutical Formulations. (n.d.). https://www.lubrizol.com/-/media/Lubrizol/Health/Literature/Mucoadhesive-Polymers-in-Pharmaceutical-Formulations.pdf

Altuntaş E, Yener G. Formulation and Evaluation of Thermoreversible In Situ Nasal Gels Containing Mometasone Furoate for Allergic Rhinitis. AAPS PharmSciTech. 2017; 18(7):2673-2682. doi: 10.1208/s12249-017-0747-8.

Bialik, M.; Kuras, M.; Sobczak, M.; Oledzka, E. Achievements in Thermosensitive Gelling Systems for Rectal Administration. Int. J. Mol. Sci. 2021, 22, 5500. https://doi.org/10.3390/ijms22115500

Church, D. J., & Nichols, A. (2017). Topical compositions comprising carbomer for the treatment and prevention of viral infections and allergic conditions (Patent No. WO2017212422A1). US Patent and Trademark Office. https://patents.google.com/patent/WO2017212422A1/en

Three Unique Topical Applications for Carbopol® Polymers: A Literature Evaluation